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Methylphenidate Amplifies the Potency and Reinforcing Effects of Amphetamines by Increasing Dopamine Transporter Expression

Overview
Journal Nat Commun
Specialty Biology
Date 2013 Nov 7
PMID 24193139
Citations 38
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Abstract

Methylphenidate (MPH) is commonly diverted for recreational use, but the neurobiological consequences of exposure to MPH at high, abused doses are not well defined. Here we show that MPH self-administration in rats increases dopamine transporter (DAT) levels and enhances the potency of MPH and amphetamine on dopamine responses and drug-seeking behaviours, without altering cocaine effects. Genetic overexpression of the DAT in mice mimics these effects, confirming that MPH self-administration-induced increases in DAT levels are sufficient to induce the changes. Further, this work outlines a basic mechanism by which increases in DAT levels, regardless of how they occur, are capable of increasing the rewarding and reinforcing effects of select psychostimulant drugs, and suggests that individuals with elevated DAT levels, such as ADHD sufferers, may be more susceptible to the addictive effects of amphetamine-like drugs.

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References
1.
Kohut S, DeCicco-Skinner K, Johari S, Hurwitz Z, Baumann M, Riley A . Differential modulation of cocaine's discriminative cue by repeated and variable stress exposure: relation to monoamine transporter levels. Neuropharmacology. 2012; 63(2):330-7. PMC: 3372622. DOI: 10.1016/j.neuropharm.2012.03.012. View

2.
Silverman P, Ho B . The discriminative stimulus properties of 2,5-dimethoxy-4-methylamphetamine (DOM): differentiation from amphetamine. Psychopharmacology (Berl). 1980; 68(3):209-15. DOI: 10.1007/BF00428105. View

3.
Roberts D, Loh E, Vickers G . Self-administration of cocaine on a progressive ratio schedule in rats: dose-response relationship and effect of haloperidol pretreatment. Psychopharmacology (Berl). 1989; 97(4):535-8. DOI: 10.1007/BF00439560. View

4.
Di Chiara G, Imperato A . Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A. 1988; 85(14):5274-8. PMC: 281732. DOI: 10.1073/pnas.85.14.5274. View

5.
Oleson E, Richardson J, Roberts D . A novel IV cocaine self-administration procedure in rats: differential effects of dopamine, serotonin, and GABA drug pre-treatments on cocaine consumption and maximal price paid. Psychopharmacology (Berl). 2010; 214(2):567-77. PMC: 3289955. DOI: 10.1007/s00213-010-2058-6. View